Azo compounds



- Patented Feb. 1939 PATENT OFFICE lizo comounps Fritz Mietrsch and Jose! Klarer, Wuppcrtal-Elberfeld, Germany, assignors to Winthrop Chemical Company, Inc., New York, N. Y., a corporation of New York No Drawing. Application January 29, 1937, Se-

Y rial No. 122,982. In Germany April 18,1934

Claims. (01. 260-155) stands for a cyclic radical containing nitrogen.

in basic linkage, that is for an aminobenzene, aminonaphthalene, pyridine, quinoline or isoquinoline radical which contains at least one ther basic nitrogen atom in the form of an amino or alkylamino group. It is stated in the said specification that acid groups should not be present in the said azo compounds since it has been established that the bactericidal activity of the azo compounds specified is reduced to a farreaching extent by the presence of acid groups.

For instance, the 2.4-diaminoazobenzene-4rwve-sulionic acid amide becomes inaclgie by th introduction of a carbo xyh'c acidgroup in the 2'- l os1tion. 'Ihisoehaviour of the said azo combounds was disadvanta eous in so far r r E as a g eate olubility of the said azo compounds was desired for their parenteral'administration, since the introduction of acid groups is known as a medium which is suitable to effect a 'greater solubility of a chemical compound. For the above-mentioned reason first it appeared necessary in the present case to take other ways in order to eflect an increase of the solubility of the azo compounds specified above. However, we have made the surprising discovery that the introduction of acid groups into the azo compounds mentioned does not in every case reduce their bactericidal ac- 40 tivity. Rather, products of increased solubility and maintained bactericidal activity are obtained if acid groups are introduced into that radical of the azo compounds which contains the basic nitrogen atoms. The cyclic radical containing the acid group and the basic nitrogen atoms, but only this radical, may also contain a hydroxyl group instead of one basic nitrogen atom. Regarding the activity and solubility it is immaterial whether the free acid group is present in the form of nucleo-bound sulfonic or carboxylic' groups; or whether these groups are bound by means of intermediate members, for instance, also aminomethane sulfonic acid, aminoacetic, hydroxy acetic, aminoethane sulfonic acid and other radicals may be introduced to eflect an increased solubility. The amino or hydroxyl groups whichare characteristic substituents of the one radical attached to the azo group may serve as intermediate members. Accordingly, new products which display a considerable bactericidal activity and a good solubility in water are obtainable by the manufacture of azo compounds of the formula: 1'\t -N=N---R. wherein R stands for a cyclic radical selected from the group consisting of para-suliamide and dlsuliamide substituted pheriyl radicals, in which radical the amino group of the sulfamide groups may be substituted by alkyl groups or an alkylene group, and wherein It stands for a cyclic radical con- 'taining nitrogen selected from the groupcon'sisting of pyridine and quinoline radicals, which radicals contain at least one further basic nitrogen atom in the form of an aminoor alkylamino group or contain at least one hydroxyl group, and further contain at leastone acid group which may be a substituent oi the amino or hydroxyl group. In these compounds the amino group attached to the sulfonic acid group(s) may be a primary, secondary or tertiary amido group. It

may be substituted by alkyl groups, such as methyl, ethyl, propyl and butyl, or by an alkylene group, such as the tetramethylene and pentamethylene group, in which case the amido group forms a pyrrolidyl or piperidyl nucleus. However, it may be expressly stated that hydroxyalkyl groups should not be present since they strongly reducethe bactericidal activity contrary to the other substituents. The benzene radical bearing the sulfonic acid amide group(s) may contain further substituents, for instance, alkyl groups, such as methyl and ethyl, but free acid groups should not be present in this radical.

The amino group which is present in the other radical attached to the azo group may be substituted by alkyl groups, such as methyl, ethyl and butyl groups, by acyl groups, such as acetyl without the bacteficidal activity of the azo compounds being substantially affected. Correspondingly the term amino when used in the appended claims is intended to include also such substi- Y a diethylamine, dihydrmethylamine. ethylene- 7 least one hydroxyl group, and further contain at least one acid group which may be a substituent of the amino or hydroxyl group, with a diazo compound selected from the group consisting of parasulfamide anddisuliamide substituted diazo compounds of the benzene series in which the amino group of the sulfamide group may be substituted by allwl groups or by an alkylene group. The

- reaction is advantageously carried ,out in the presence of waterat a low temperature, say at about 20 C. or below.

The azo compounds thus obtainable are colored powders which in'the form of their alkali or alkaline-earth metal-, ammonium or amine salts in. general are soluble in water. In view of their considerable bactericidal activity they have proved active in the, treatment of infectious diseases. The invention is further illustrated by the iollowing examples without being restricted thereto: a

Example 1.20.8 grams of the hydrochloride oi 4-aminobenzene sulfonic acid amide are dissolved ,in 12% cos, of cencentrated, hydrochloric acid and water and diazotized with a concentrated precipitates as a yellow precipitate which is filtered aqueous solutions of 6.9 grams of sodium nitrite at to 5 C. The solution is mixed with an acetic acid solution of 27.1 grams of 2.6-diaminopyridine-disulionic acid (prepared by heating 12.6- diamino-pyridine in 20% fuming sulfuric acid with the addition of vanadylsulfate). After the addition of sodium acetate and after prolonged stirring the am compound of the formula";

with. suction and dissolved in dilute caustic soda solution. From the intensely yellow colored alkaline solution the azo compound is precipitated bymeansoiacids.

Example 2.-26 grams of the sodium salt of 6- aminoquinoline-H-methane sulfonic acid (yellow,

readily water-soluble powder, obtained by heating fi-aminoquinoline with sodimn formald hy e bisuliite) are added to the diazo solution from 20.8 grams of the hydrochloride of 4-aminobenzene-sulfonic acid amide which has been neutralized with sodium bicarbonate. From the intensely orange colored solution to which alcohol has been added the readily water-soluble yellow I v precipitates in the-form of a brown red crystal red sodium salt of compound of the formula 3 readily soluble in water prepared by heating 6- aminoquinoline with sodium formaldehyde sulfogwlate) a deep yellow, readily water-soluble azo compound being obtained: Or by 20.4 grams of quinoline-6-amino-acetic acid (prepared by heating fi-aminoquinoline with chloroacetic acid). A Vermilion red azo compound is obtained which is insoluble in water as free acid. In sodium carbonate solution it turns to dark orange. By means of sodium chloride the sodium salt may be obtained in red needles.

Example 3.20 grams of 4-aminobenzene-sulionic acid monoethylamide. are dissolved in 30 cos. of concentrated hydrochloric acidand 100 cos. of water anddiazotized with 8.5'grams' of potassium nitrite. The diazo solution is then added to a solution of 18.9 grams of 8-hydroxy-' quinoline-l-carboxylic acid in potassium carbonate solution. The potassium salt of the 8- hydroxyquinoline-Z-carboxylic acid-azophenyl- 4 '-sulionicacid-ethylamide oi the formula 655/A ficultly soluble in water. After isolation it may be transformed into its calcium,- magnesium,-

lithium-, orammonium salt by treatment with I the corresponding hydroxides.

Instead of the 4-aminobenzene sulfonic acidmonoethylamide the .2-methyl-4-aminobenzene sulfonic acid amide may be used.

Example 4.-=l.'l.2 grams of 4 -aminobenzene sulfonic acid amide are dissolved in 25 cos. of concentrated hydrochloric acid and water and diazotized with an aqueous solution of 6.9 grams .or sodium nltriteat 0 to 5 c. J The diazo solution is added to a solution of 22.5 grams of 8- hydrox'yquinoline-B-sulfonic acid in 400 cos. of 10% sodium carbonate solution. After coupling is complete the mixture is acidified with dilute acetic acid. Thereby the 4'-sulfonami de-phenylazo-8-hydroxyquinoline-5-sulfonic acid of the. formula 1 1 powder which is diiiicultly soluble in water. In dilute. caustic soda solution and sodium carbonate solution it is taken up with a yellowish-red, in

dilute hydrochloric acid with rose-red coloration.

Example 5.-1'7.2 grams of 4-aminobenz'ene sulionic acid amide are as described above and mixedqvitlr a solution of 19.0 grams of 4-hydroxy-6-aminoquinoline-2-carboxylic acid (yellow crystals melting above 300C. whichdissolve in sodium' carbonate solution and hydrochloric acid) in 400 cos. of 10% sodium carbonate solution. On acidification with aceticacid the 4'- sulionic acid amide-phenylazo-4-hydroxy-6- aminoquinoline-2-carboxylic acid of the formula newts-Oaks on HsN C O OH from 18.9 grams of 8-hydroxyquinoline-7-carboxylic acid or from 21.8 grams of B-aminoquinoline-fi-hydroxy-acetic acid (obtained by reaction acid and reduction of the nitro compound) the 4' sulfonic acidamide-phenylazo 8 hydroxyquino line-'I-carboxylic acid or the 4' -sulfonicacidamide-phenylazo-8-aminoquinoline- 6 -hydroxyacetic acid as a brownish red crystal powder meltof B-hydroxy-il-nitroquinoline with chloro-aceti? ing above 300 0.

v v sod! HNOIB N= is obtained in brown red crystals melting above 300 C. Similar azo compounds are obtainedwith 20.0 grams of 4-aminobenzene sulfonic acid dimethylamidemelting at 168 0., or with 24.0 grams-oi 4-aminobenzene sulionic acid piperidide melting at 164 0., or with 30.7 grams of aminobenzene-3.5-bis (sulfonic acid dimethylamidel melting at 183 C, The latter has the formula SOIH meal.

, filed April 10, 1935 We claim:

1. A20 compounds of the general formula: I I R. 1-I=NR wherein R stands for a cyclic radical selected from the group consisting of phenyl radicals containing a 'sulfamide' group in the para-position to the azo group and of disultamide substituted phenyl radicals and of the the nitrogen atom, which radicals are free from other substituents, and wherein R stands for a cyclic radical containing nitrogen selected from the group consisting of pyridine and quinoline radicals a nuclear carbon atom of which radical is directly connected with the azo group and which radical contains at least one further substituent selected from the group consisting of amino, lower hydrocarbon alkylamino and hydroxyl groups and further contains at least one acid radical which is bound to the cyclic radical by a member selected from the group consisting 01' nuclear carbon atoms, oxygen atoms andamino groups, which azo compounds are in the form of their alkali and alkaline-earth metal-, ammoniumand amine salts in general soluble in water.

2. A20 compounds of the formula:

wherein R stands for a phenyl radical which contains a sulfamide group in the paraf-position to the azo group and is free from other substituents, and wherein R. stands for a cyclic radical containing nitrogen selected from the group consisting of pyridine and quinoline radicals, a nuclear carbon atom of which radical is directly connected with the azo group and which radical contains at least one further substituent selected from the group consisting of amino, lower hydrocarbon alkylamino and hydroxyl groups and further contains at least one acid radical which is bound to the cyclic radical by a member selected from the group consisting of nuclear carbon atoms, oxygen atoms and amino groups, which azo compounds are in the form of their alkali and alkaline-earth metal-, ammoniumand amine salts in general soluble in water.

3. A20 compoundsof the general formula:

R lf-l=l -ll=t wherein R stands for a cyclic radical selected from the group consisting of phenyl radicals containing a sulfamide group in the para-position to the azo group and of disulfamide substituted phenyl radicals and of the corresponding N- lower hydrocarbon alkyl and N-alkylene substituted products, both free valences of the alkylene radical being attached to the nitrogen atom, which radicals are free from other substituents,

and wherein R stands for a quinoline radical a nuclear carbon atom of which radical is directly connected with the azo group and which con-- trains at least one further substituent selected from thevgroup consisting of amino, lower hydrocarbon allwlamino and hydroxyl groups and further contains at least on acid radical which is bound to the quinoline radical by a member selected from the group consisting oi. nuclear carbon atoms, oxygen atoms and amino groups, which azo compounds are in the form or their alkali and alkaline-earth meta1-, ammoniumand amine salts in general soluble in water.

' 4. Azo compounds of the general formula:

wherein R stands for a phenyl radical which contains a suliamide group in the para-position to the azo group and is free from other substitu" ents', and wherein R stands for a quinoline radical a nuclear carbon atom of which radical is directly connected with the azo group and which contains at least one further substituent selected from the group consisting of amino, lower hydro-' carbon alkylamino and hydrorw'l groups and further contains at' least oneacid radical which is bound to the quinoline radical by a member selected from the group consisting of nuclear carbon atoms, oxygen atoms and amino groups,

which azo compounds are in the form of their 25 a phenyl radicals which radicals are free from aikaliand alkalineearth metal-, ammoniumand amine salts in general solublein water. 5. Azo compounds of the general formula:

wherein R stands for a phenyl radical which contains 'a sulfamide-group in the para-position to the azo group and is free from other substitu-- cuts, and R. stands for a quinoline radical substituted by a hydroxyl group and at'least one.

sulfo group. a nuclear carbon atom of which radical is directly connected with the azo'group and which azo compounds are in the form of their alkali-and alkaline-earth metal-, am-

monium and amine salts in general soluble in water.

6. A20 compounds of the general formula:

wherein R stands for a cyclic radical selected fromthe group consisting of phenyl radicals containing a sulfamide group in the para-position to the azo group and of disulfai'nide substituted other substituents, and It. stands for-a pyridine radical a nuclear carbon atom of which radical is directly connected with the azo group and lower hydrocarbon alkyl-amino and hydroxyl monium and which contains at least one furthersubstituent selected from the group consisting of amino,

groups and further contains at least one acid radical which is bound to the pyridine radical by a member selected from the group consisting m! nu-. 1

clearcarbon atoms, oxygen atoms and amino groups, which 9.20 compounds are in the form of their alkaliand alkaline-earth metal-, am-

ter amine salts in general' soluble in we. 7

l. Aao compounds of the general formula:

wherein R stands for a cyclic radical seiec from the group consisting of phenyl radicals co taming a sulfamide group in the para-position to a the azo group and of disulfamide substituted phenyl radicals which are free from other substituents, and Rlstands for an aminopyridine radical which radical is substituted by at least one acid radical, a nuclear carbon atom of which radical is directly connected with the azo group and-which azo compounds are in the form of their alkaliand alkaline-earth metal-, ammonium and amine salts in general soluble in water. r

8. The azo compound of the formula:

9. The azo compound of the formula:

10. The and compound of the formula:

mms-om-NE N mm mrzscn. aosnr man. 

